Faculty Bibliography

BACKGROUND:Patients on dialysis are particularly vulnerable to meticillin-resistant Staphylococcus aureus (MRSA) infections and MRSA colonization is associated with increased risk for severe infections in this population. AIM/OBJECTIVE:Determination of risk factors for MRSA colonization among dialysis patients. METHODS:This is a systematic review and meta-analysis of studies reporting risk factors of MRSA colonization. We performed a PubMed and EMBASE literature search to identify all studies on risk factors for MRSA colonization among patients undergoing dialysis treatment. Previous hospitalization, type of dialysis access, comorbid conditions, dialysis vintage, gender, length of time on dialysis, and previous antibiotic use were extracted and assessed for possible association with MRSA colonization in this population. FINDINGS/RESULTS:Ten out of 8252 articles, presenting data on 2364 dialysis patients, were included. We found that hospitalization within the previous 12 months [odds ratio (OR): 1.93; 95% confidence interval (CI): 1.04-3.58] and the use of temporary dialysis access (relative risk: 1.66; 95% CI: 1.06-2.60) were associated with a significantly higher risk of MRSA colonization. MRSA carriage was associated with lower serum albumin levels compared to non-carriage (OR: 0.8; 95% CI: 0.68-0.95) and was higher among patients with chronic lung disease (OR: 2.16; 95% CI: 1.04-4.51). There were no data on patients undergoing peritoneal dialysis. CONCLUSION/CONCLUSIONS:Active surveillance approaches, including potential decolonization strategies, are suggested to focus on these subgroups of haemodialysis patients with hospitalization within the previous year, temporary dialysis access, lower serum albumin levels, and chronic lung disease comorbidity.

BACKGROUND:Microbiologic cultures, the current gold standard diagnostic method for invasive Candida infections, have low specificity and take up to 2-5 days to grow. We present the results of the first extensive multicenter clinical trial of a new nanodiagnostic approach, T2 magnetic resonance (T2MR), for diagnosis of candidemia. METHODS:Blood specimens were collected from 1801 hospitalized patients who had a blood culture ordered for routine standard of care; 250 of them were manually supplemented with concentrations from <1 to 100 colony-forming units (CFUs)/mL for 5 different Candida species. RESULTS:T2MR demonstrated an overall specificity per assay of 99.4% (95% confidence interval [CI], 99.1%-99.6%) with a mean time to negative result of 4.2 ± 0.9 hours. Subanalysis yielded a specificity of 98.9% (95% CI, 98.3%-99.4%) for Candida albicans/Candida tropicalis, 99.3% (95% CI, 98.7%-99.6%) for Candida parapsilosis, and 99.9% (95% CI, 99.7%-100.0%) for Candida krusei/Candida glabrata. The overall sensitivity was found to be 91.1% (95% CI, 86.9%-94.2%) with a mean time of 4.4 ± 1.0 hours for detection and species identification. The subgroup analysis showed a sensitivity of 92.3% (95% CI, 85.4%-96.6%) for C. albicans/C. tropicalis, 94.2% (95% CI, 84.1%-98.8%) for C. parapsilosis, and 88.1% (95% CI, 80.2%-93.7%) for C. krusei/C. glabrata. The limit of detection was 1 CFU/mL for C. tropicalis and C. krusei, 2 CFU/mL for C. albicans and C. glabrata, and 3 CFU/mL for C. parapsilosis. The negative predictive value was estimated to range from 99.5% to 99.0% in a study population with 5% and 10% prevalence of candidemia, respectively. CONCLUSIONS:T2MR is the first fully automated technology that directly analyzes whole blood specimens to identify species without the need for prior isolation of Candida species, and represents a breakthrough shift into a new era of molecular diagnostics. CLINICAL TRIALS REGISTRATION/BACKGROUND:NCT01752166.

OBJECTIVES/OBJECTIVE:It has been suggested that colonization with C. difficile protects from infection. Nevertheless, the association between carriage of toxinogenic strains and ensuing C. difficile infections (CDIs) has not been studied. METHODS:We searched PubMed and EMBASE databases up to 20 June 2014, using the term "difficile". Our primary outcomes of interest included the prevalence of isolation of toxinogenic C. difficile or its toxins from asymptomatic patients on hospital admission through stool or rectal swab testing and the risk of ensuing infection among colonized and noncolonized patients. Data on previous hospitalization, antibiotic, and proton pump inhibitor (PPI) use and prior CDIs among colonized and noncolonized patients were also extracted. RESULTS:Nineteen out of 26,081 studies on 8,725 patients were included. The pooled prevalence of toxinogenic C. difficile colonization was 8.1% (95% confidence interval (CI) 5.7-11.1%), with an increasing trend over time (P=0.003), and 10.0% (95% CI 7.1-13.4%) among North American studies. Patients colonized upon hospital admission had a 5.9 times higher risk of subsequent CDIs compared with noncolonized patients (relative risk (RR) 5.86; 95% CI 4.21-8.16). The risk of CDI for colonized patients was 21.8% (95% CI 7.9-40.1%), which was significantly higher than that of noncolonized patients (3.4%; 95% CI 1.5-6.0%; P=0.03), with an attributable risk of 18.4%. History of hospitalization during the previous 3 months was associated with a higher risk of colonization (RR 1.63; 95% CI 1.13-2.34), as opposed to previous antibiotic (RR 1.07; 95% CI 0.75-1.53) and PPI use (RR 1.44; 95% CI 0.94-2.23), as well as history of CDI (RR 1.45; 95% CI 0.66-3.18) that had no impact. CONCLUSIONS:Over 8% of admitted patients are carriers of toxinogenic C. difficile with an almost 6 times higher risk of infection. These findings update current knowledge regarding the contribution of colonization in CDI epidemiology and stress the importance of preventive measures toward colonized patients.

OBJECTIVES/OBJECTIVE:ICUs are a major reservoir of methicillin-resistant Staphylococcus aureus. Our aim was to estimate costs and effectiveness of methicillin-resistant Staphylococcus aureus prevention policies. DESIGN AND INTERVENTIONS/METHODS:We evaluated three up-to-date methicillin-resistant Staphylococcus aureus prevention policies, namely, 1) nasal screening and contact precautions of methicillin-resistant Staphylococcus aureus-positive patients; 2) nasal screening, contact precautions, and decolonization (targeted decolonization) of methicillin-resistant Staphylococcus aureus carriers; and 3) universal decolonization without screening. We implemented a decision-analytic model with deterministic and probabilistic analyses. Methicillin-resistant Staphylococcus aureus infections averted, quality-adjusted life years gained, and incremental cost-effectiveness ratios were calculated. Cost-effectiveness planes and acceptability curves were plotted for various willingness-to-pay thresholds to address uncertainty. MEASUREMENTS AND MAIN RESULTS/RESULTS:At base-case scenario, universal decolonization was the dominant strategy; it averted 1.31% and 1.59% of methicillin-resistant Staphylococcus aureus infections over targeted decolonization and screening and contact precautions, respectively, and saved $16,203/quality-adjusted life year over targeted decolonization and 14,562/quality-adjusted life year over screening and contact precautions. Results were robust in sensitivity analysis for a wide range of input variables. In probabilistic analysis, universal decolonization increased quality-adjusted life years by 1.06% (95% CI, 1.02-1.09) over targeted decolonization and by 1.29% (95% CI, 1.24-1.33) over screening and contact precautions; universal decolonization resulted in average savings of $172 (95% CI, $168-$175) and $189 (95% CI, $185-$193) over targeted decolonization and screening and contact precautions, respectively. With willingness-to-pay threshold per quality-adjusted life year gained ranging from $0 to $50,000, universal decolonization was dominant over targeted decolonization in 67.5-75.4% and dominant over screening and contact precautions in 66.0-75.4%. CONCLUSIONS:In the ICU setting, universal decolonization outperforms the other two strategies and is likely to be cost-effective even at low willingness-to-pay thresholds. Assuming 700 annual ICU admissions in an average 12-bed ICU, the projected annual savings reach $129,500 to $135,100.

BACKGROUND:Vancomycin-resistant enterococci (VRE) have become important nosocomial pathogens causing outbreaks worldwide. Patients undergoing dialysis represent a vulnerable population due to their comorbid conditions, frequent use of antibacterial agents, and frequent contact with health care settings. STUDY DESIGN/METHODS:Systematic review and meta-analysis of cross-sectional studies of screening for VRE colonization. SETTING & POPULATION/METHODS:Patients receiving long-term dialysis treatment. SELECTION CRITERIA FOR STUDIES/METHODS:We performed a systematic literature search of PubMed and EMBASE databases to identify studies performing screening for VRE colonization among dialysis patients. PREDICTOR/METHODS:Region, recent use of vancomycin or other antibiotics, previous hospitalization. OUTCOMES/RESULTS:(1) VRE colonization and (2) rate of VRE infection among colonized and noncolonized individuals. Relative effects were expressed as ORs and 95% CIs. RESULTS:We identified 23 studies that fulfilled the inclusion criteria and provided data for 4,842 dialysis patients from 100 dialysis centers. The pooled prevalence of VRE colonization was 6.2% (95% CI, 2.8%-10.8%), with significant variability between centers. The corresponding number for North American centers was 5.2% (95% CI, 2.8%-8.2%). Recent use of any antibiotic (OR, 3.62; 95% CI, 1.22-10.75), particularly vancomycin (OR, 5.15; 95% CI, 1.56-17.02), but also use of antibiotics other than vancomycin (OR, 2.92; 95% CI, 0.99-8.55) and recent hospitalization (OR, 4.55; 95% CI, 1.93-10.74) significantly increased the possibility of a VRE-positive surveillance culture. Colonized patients had a significantly higher risk of VRE infection (OR, 21.62; 95% CI, 5.33-87.69) than their noncolonized counterparts. LIMITATIONS/CONCLUSIONS:In 19 of 23 studies, a low percentage of dialysis patients (<80%) consented to participate in the screening procedure. 4 of 8 studies in which patients were followed up for more than 1 month reported VRE infections and only 5 of 23 studies provided extractable data for antibiotic consumption prior to screening. CONCLUSIONS:VRE colonization is prevalent in dialysis centers. Previous antibiotic use, in particular vancomycin, and recent hospitalization are important predicting factors of colonization, whereas the risk of VRE infection is significantly higher for colonized patients.